B3.041 Prework Intro to Lymphoid Neoplasms Flashcards
where can lymphoid neoplasms be derived from?
precursor cells (B or T ALL)
mature B cells
mature T/MK cells
where can lymphoid neoplasms present?
primarily bone marrow/blood
primarily in lymph nodes
primarily in extranodal tissues
how are lymphoid neoplasms classified
cell of origin
development stage of transformed cell (precursor or mature)
clinical, immunophenotypic, genetic, and molecular findings
DOES NOT distinguish primarily blood/BM (leukemia) from primarily lymph node/tissue presentation (lymphoma)
same as chronic lymphocytic leukemia
small lymphocytic lymphoma
same as acute lymphoblastic leukemia
lymphoblastic lymphoma
what % of all lymphoid neoplasms involve B cells
80%
what % of all lymphoid neoplasms involve T/NK cells
20%
what type of lymphoma is classified neither as T or B cell?
Hodgkin
what are the 5 most common non-Hodgkin lymphomas?
diffuse large B cell lymphoma follicular lymphoma MALT lymphoma mature T cell lymphomas CLL/SLL
which 3 mature B cell neoplasms occur in the BM/blood
CLL/SLL
hairy cell leukemia
Burkitt
which 5 mature B cell neoplasms occur in the lymph nodes
CLL/SLL follicular lymphoma diffuse large B cell lymphoma mantle cell lymphoma Burkitt
which 2 mature B cell neoplasms occur extranodally
diffuse large B cell lymphoma
marginal zone lymphoma
which 2 mature T cell neoplasms occur in the BM/blood
adult T cell leukemia/lymphoma
mycosis fungoides/Sezary syndrome
which 3 mature T cell neoplasms occur in the lymph nodes
peripheral T cell lymphoma, unspec
anaplastic large cell lymphoma
adult T cell leukemia/lymphoma
which mature T cell neoplasm occurs extranodally
mycosis fungoides/ Sezary syndrome
what are some immunophenotypic markers of mature B neoplasms
CD19, CD20
monoclonal surface Ig (K or L restricted)
others disease based
what are some immunophenotypic markers of mature T neoplasms
CD2, CD3, CD5, CD7 (some may be absent)
CD4 and/or CD8 (variable, do NOT establish clonality)
others diseased based
genetic features of mature B neoplasms
monoclonal rearranged Ig genes
translocations involving chromosome 14 (IgH gene locus, constitutively expressed)
disease specific findings
genetic features of mature T neoplasms
monoclonal rearranged T-cell receptor genes (a/B or y/d)
disease specific findings
what are 2 different possible lymph node architectures of lymphoid neoplasms?
diffuse
nodular/follicular
distinguish between small and medium-large cell lymphoid neoplasms
small
-more indolent
-immunophenotype and genetics are critical for diagnosis and classification
medium-large
-tend to be more aggressive
-morphology supplemented by immunophenotype and genetics for diagnosis and classification
clinical features of chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL)
older adults most common leukemia in the US variable anemia, thrombocytopenia lymphadenopathy immunologic abnormalities- autoimmune anemia or thrombocytopenia, monoclonal immunoglobulin (paraprotein)
morphology of CLL/SLL
CLL - small mature lymphocytes in blood, BM
SLL- diffuse infiltrates of small lymphocytes in lymph nodes
histologic features of CLL/SLL
smudge like cells w no cytoplasm
immunophenotype of CLL/SLL
CD19+
CD20+
CD5+
sIg+ (clonal)
genetics of unmutated CLL/SLL (U-CLL/SLL)
no somatic hypermutation in IgV
40-50% of cases
unfavorable
genetics of mutated CLL/SLL (M-CLL/SLL)
somatic hypermutation in IgV
50-60% of cases
favorable
course and prognosis of CLL/SLL
median survival 6 y -worse for U-CLL/SLL (3) than M-CLL/SLL (7) prolymphocytic transformation - 15-30% -mean survival <2 y Richter transformation - 5-10% -large cell lymphoma -increased lymphadenopathy -mean survival <1 y
clinical features of hairy cell leukemia
middle aged and older adults
rare
splenomegaly, hepatomegaly
pancytopenia, infections
morphology/histological features of hairy cell leukemia
villous projections
immunophenotype of hairy cell leukemia
CD19+ CD20+ sIg+ (clonal) CD11c+ CD25+ CD103+ ** annexin A1 ** **very specific
genetics of hairy cell leukemia
BRAF mutation
also seen in other cancers, targeted therapies exist
course and prognosis of hairy cell leukemia
indolent
clinical features of follicular lymphoma
middle aged and older adults
common (2nd most common non Hodgkin)
lymphadenopathy
hepatosplenomegaly
morphology of follicular lymphoma
nodular infiltrate of small cleaved lymphocytes in lymph nodes
diminished mantle zone
absent tangible body macrophages
immunophenotype of follicular lymphoma
CD19+
CD20+
CD10+
sIg+ (clonal)
genetics of follicular lymphoma
t(14;18)
overexpression of BCL2 which prevents apoptosis
course and prognosis of follicular lymphoma
indolent
clinical features of mantle cell lymphoma
middle aged and older adults
uncommon
lymphadenopathy
hepatosplenomegaly (often advanced stages)
morphology of mantle cell lymphoma
nodular or diffuse infiltrate of small lymphocytes in lymph nodes
immunophenotype of mantle cell lymphoma
CD19+ CD20+ CD5+ sIg+ (clonal) above same as CLL/SLL cyclin D1+
genetics of mantle cell lymphoma
t(11;14) overexpression of cyclin D1
involved in cell division (oncogene)
course and prognosis of mantle cell lymphoma
poor prognosis
median survival 3-4 y
unusually aggressive for small cell
clinical features of marginal zone lymphoma
extranodal - GI tract, lung, skin, eye, head & neck
association with immune reaction and chronic infection (H. pylori)
-can sometimes be treated early by treating underlying infection
morphology of marginal zone lymphoma
infiltrate of lymphoid cells into epithelium and expanded marginal zone
immunophenotype of marginal zone lymphoma
CD19+
CD20+
sIg+ (clonal)
course and prognosis of marginal zone lymphoma
indolent
clinical features of diffuse large B cell lymphoma
middle aged and older adults most common lymphoma lymphadenopathy hepatosplenomegaly frequently extranodal
morphology of diffuse large B cell lymphoma
diffuse infiltrate of large lymphocytes in lymph nodes
immunophenotype of diffuse large B cell lymphoma
CD19+ CD20+ CD10+/- sIg+ (clonal) some types associated with EBV or HHV8
genetics of diffuse large B cell lymphoma
may be positive for MYC translocation (most aggressive)
course and prognosis of diffuse large B cell lymphoma
aggressive
clinical features of Burkitt
rapidly progressive tumor mass -extremely high growth fraction -tumor lysis syndrome common w treatment -fast, but responsive to treatment endemic form in Africa -primarily kids - >95% associated with EBV -mandible, abdomen sporadic form in US -involved kids and adults -15-20% associated with EBV -abdomen HIV associated form -worst response to therapy -25% associated with EBV
morphology of Burkitt
diffuse infiltrate of medium sized lymphocytes in lymph nodes
high mitotic rate
tingible body macrophages (starry sky)
immunophenotype of Burkitt
CD19+ CD20+ CD10+ sIg+ (clonal) TdT- (can look like ALL, but ALL is TdT+)
genetics of Burkitt
t(8;14) [variants t(2;8) or t(8;22)] MYC oncogene translocated to IgH locus and constitutively expressed
course and prognosis of Burkitt
highly aggressive course but high cure rates (60-90%) w chemotherapy
clinical features of mycosis fungoides/sezary syndrome
older adults
cutaneous patch, plaque, nodule stages
lymphadenopathy unusual
morphology of MF/SS
MF- dermal infiltrate of atypical lymphocytes with epidermotropism and Pautrier microabcesses
SS- circulating lymphoid cells with cerebriform nuclei and erythroderma
immunophenotype of MF/SS
CD4+ T cells
course and prognosis of MF/SS
indolent
chronic course with 90% 5 year survival
SS more aggressive form
clinical features of adult T cell leukemia/lymphoma
endemic in Japan, Caribbean, West Africa
middle aged to older adults
caused nu HTLV-1 infection
generalized lymphadenopathy, skin lesion, hepatosplenomegaly, lymphocytosis, and hypercalcemia
course and prognosis of adult T cell leukemia/lymphoma
poor prognosis especially in leukemic phase
clinical features of anaplastic large cell lymphoma
lymphadenopathy
immunphenotype of anaplastic large cell lymphoma
CD30+
genetics of anaplastic large cell lymphoma
t(2;5) rearrangement of ALK
course and prognosis of anaplastic large cell lymphoma
poor prognosis if ALK-
clinical features of peripheral T-cell lymphoma
lymphadenopathy fever pruitis weight loss eosinophilia (secretion of IL-5)
course and prognosis of peripheral T cell lymphoma
poor prognosis with 20-30% 5 year survival rate
clinical features of Hodgkin
bimodal age distribution (15-35 and >50)
most common malignancy in 10-30 y age group in US
lymphadenopathy, splenomegaly
constitutional (“B”) symptoms- fever, night sweats, weight loss
immune dysfunction
possible relation to EBV
morphology of Hodgkin
classical - Reed-Sternberg cells in a polymorphous cellular background
nodular lymphocyte predominance - no Reed-Sternberg cells; large B cells in a background of small lymphocytes
describe Reed-Sternberg cells
extremely large
2 nuclei
large nucleous with clearing around it
what are some features that make Hodgkin unique from non-hodgkin
heterogeneous population reed-Sternberg primary extranodal presentation rare often localized to a single nodal group spread along contiguous nodal groups tonsils and adenoids rarely involved young adults and elderly good prognosis
immunophenotype of Hodgkin
reed Sternberg cells CD15+ CD30+ CD20+/- negative for most other T cell markers
genetics of Hodgkin
mutate germinal center B cells that escape apoptotic death
course and prognosis
excelled prognosis in early stage (90% cure rate)
risk of secondary malignancy in long term survivors (due to chemo and radiation)
non-neoplastic proliferations of lymphocytes
viral infections
acute bacterial infections
chronic bacterial infections
atypical lymphocytes
non-neoplastic lymphadenopathy
follicular hyperplasia- infection, autoimmune disorders, drug reaction
paracortical hyperplasia- viral infections, drug reactions
sinus histiocytosis- lymph nodes draining infections of cancer